Alkylmagnesium amides

A useful application of organomagnesium amides is in the enantioselective conjugate addition to enamidomalonate to prepare /3-amino acid derivatives (Scheme 16). The alkylmagnesium amide complexes provided both high yields and high selectivity in the organic transformation. 

As can be seen from the structure, the dimerization proceeds via nitrogen-magnesium interactions. To our knowledge, dimerization via Mg—R—Mg two-electron three-center bonds in alkylmagnesium amides has neither previously been found in the solid state nor proved by X-ray techniques, although the existence of such bonds has been claimed (10). 

Eaton s base also has stimulated use of an enantiopure alkylmagnesium amide for enantioselective deprotonation of a set of 4-substituted cyclohexanones (equation 36) further work in this area can be expected. Einally, efficient ortho-magnesiation of A-phenylsulfonylpyrrole has been achieved with an excess of (PrMgCl and a catalytic amount (5mol%) of (Pr2NH to serve as a proton transfer agent subsequent reaction with a range of electrophiles afforded decent yields of products (equation 37). ... 

Several routes to Mg bisamides have been developed. These include the direct reaction between the metal and a protic amine, a variety of transmetalation strategies, disproportionation of alkylmagnesium amides, and transamination reactions (Scheme 3.32). On the other hand, the most straightforward and most routine synthesis involves the reaction of a dialkylmagnesium with two equivalents of amine. In some instances the amination reaction ceases after transfer of one amino function but gentle heating of the reaction mixture is usually sufficient to ensure complete conversion to the bisamide. Without doubt this route is now the method of choice, because ether-free Bu2Mg (supplied as a 1 1 mixture of n- and s-butyl, with 5% n-octyl, in heptane) has become commercially available (Aldrich). 

The mechanism of CO2 fixation by alkylmagnesium amides and magnesium bisamides has been analyzed by Himmel [132] with the aid of quantum chemical calculations relying on pure DFT (BP86)... 

Improved yields of cyclopropylamines 47 could be obtained by using methyltitanium triisopropoxide (53) instead of titanium tetraisopropoxide [108], as well as by adding the Grignard reagent to the mixture of the amide and the titanium reagent at ambient rather than low temperature (Schemes 11.15 and 11.16, and Table 11.9) [67,69]. In principle, methyltitanium triisopropoxide requires only one equivalent of the alkylmagnesium halide to generate a dialkyltitanium diisopropoxide intermediate 55, and in this particular case P-hydride elimination can only occur at the non-methyl substituent so that methane... 

In the hydroxycyclopropanation of alkenes, esters may be more reactive than N,N-dialkylcarboxamides, as is illustrated by the exclusive formation of the disubstituted cyclopropanol 75 from the succinic acid monoester monoamide 73 (Scheme 11.21) [91]. However, the reactivities of both ester- as well as amide-carbonyl groups can be significantly influenced by the steric bulk around them [81,91]. Thus, in intermolecular competitions for reaction with the titanacydopropane intermediate derived from an alkylmagnesium halide and titanium tetraisopropoxide or methyltitanium triisoprop-oxide, between N,N-dibenzylformamide (48) and tert-butyl acetate (76) as well as between N,N-dibenzylacetamide (78) and tert-butyl acetate (76), the amide won in both cases and only the corresponding cyclopropylamines 77 and 79, respectively, were obtained (Scheme 11.21) [62,119]. 

In contrast to the metallation with alkyllithium or alkali amides, Grignardation of HOCR with alkylmagnesium halide is not an instantaneous reaction. The more acidic 1,3-diynes and hetero-subsdtuled acetylenes react most readily. In the other cases heating for several minutes... 

Aldehyde imines derived from alkoxyamines are metalated by LDA (0 °C, TIIF, 1 h6 or —23 °C, THF, 0.5 h13) and by potassium diethylamide, lithium bis(trimethylsily])amide and lithium 2,2,6,6-tetramethylpiperidide (—23 °C, THF, 2-4 h)1J. Nucleophilic bases such as alkyl- and aryllithium derivatives and, in some cases, alkylmagnesium bromides add to aldehyde imines. Best enantioselectivities are achieved with lithium 2,2,6,6-tetramethylpiperidide (LTMP)13. The... 

Formation of cyclopropylamines and cyclopropanols from alkylmagnesium halides and esters, amides, or nitriles, catalyzed by titanium alcoholates, was discovered by Kulinkovich in 1989. The reaction mechanism includes the formation of dialkoxytitanacyclopropanes, which reacts with a carbonyl compound or a nitrile (Scheme 109). 

Detailed reviews on the structures of organomagnesium compounds and the constitution of their solutions have been published [D, 1, 2]. These references, especially the first two, also cover alkylmagnesium hydrides, amides, alkoxides and thiolates. However, while all of these compounds are of intrinsic interest, they are little used in synthesis. 

For application in synthesis, the most important of these are those where X = halogen and Y = alkyl the transformation of Grignard reagents into dialkylmagnesium compounds. Other transformations of this type are valuable for preparing alkylmagnesium hydrides (Y = H), alkoxides (Y = OR ), carboxylates (Y = OCOR ), amides (Y = NR 2, thiolates (Y = SR ), etc., but since most of these products are not extensively employed in synthesis these transformations are summarized only briefly. 

With a dialkylmagnesium compound, one equivalent of the proton donor gives an alkylmagnesium alkoxide (thiolate, amide) (see Section 3.4.4), whereas 0.5 equivalent gives the magnesium alkoxide (thiolate, amide) ... 

Alkylmagnesium halide Carboxylic acid amides from esters Bodroux reaction... 

The reactions of alkylmagnesium reagents with sterically hindered amines in THF lead to the formation of magnesium amides 56-58,which react with C-H acidic substrates much faster than alkylmagnesium reagents (Scheme 2-25). 

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